Non-polio enterovirus aseptic meningitis in infants up to three months of age, the bacterial mask of viral disease: A retrospective cohort study

Nadeen Makhoul; Imad Kassis; Manfred S Green; Rozeen Abu Shqara; Ranaa Damouni Shalabi; Moran Szwarcwort Cohen; Halima Dabaja-Younis

doi:10.1016/j.jcv.2023.105427

Non-polio enterovirus aseptic meningitis in infants up to three months of age, the bacterial mask of viral disease: A retrospective cohort study

J Clin Virol. 2023 May:162:105427. doi: 10.1016/j.jcv.2023.105427. Epub 2023 Mar 24.

Authors

Nadeen Makhoul¹, Imad Kassis², Manfred S Green³, Rozeen Abu Shqara¹, Ranaa Damouni Shalabi⁴, Moran Szwarcwort Cohen⁵, Halima Dabaja-Younis⁶

Affiliations

¹ Pediatric Department, Rambam Health Care Campus, Haifa, Israel.
² Pediatric Department, Rambam Health Care Campus, Haifa, Israel; The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³ University of Haifa, Faculty of Public Health, Department of Epidemiology, Haifa, Israel.
⁴ Pediatric Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel.
⁵ Microbiology Laboratory, Rambam Health Care Campus, Haifa, Israel.
⁶ The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Pediatric Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel. Electronic address: h_dabaja@rambam.health.gov.il.

PMID: 37001461
DOI: 10.1016/j.jcv.2023.105427

Abstract

Background: Non-polio enterovirus aseptic meningitis (NPE-AM) is a self-limiting illness that can mimic serious bacterial infection (SBI) in infants during their first months of life.

Objectives: To compare the clinical features of febrile infants diagnosed with NPE-AM with those of infants who had SBI or non-bacterial infection (NBI).

Study design: A systematic series of febrile infants < 3-months-old hospitalized between 2010 and 2019 with febrile illness in a tertiary hospital. Clinical and laboratory data were compared between the three groups.

Results: Overall 1278 infants were included; 207 (16.2%) had NPE-AM, 210 (16.4%) SBI and 861 (67.4%) NBI. The median age was 34 (IQR: 21.5-51.7) days. NPE-AM was documented in 25% of infants < 29 days and 9.9% of infants aged 29-90 days. Infants with NPE-AM or SBI had fever >39°C more frequently, 24.2% and 17.1% compared with 10% in infants with NBI (p < 0.001). Fever duration ≥ 2 days was reported in 3.4% of infants with NPE-AM vs 18.6% in SBI and 26.3% in NBI (p < 0001); rash occurred in 37.7% in NPE-AM compared to 4.6% in NBI and 5.7% in SBI (p < 0.001). The mean white blood count, C-reactive protein and absolute neutrophil count were significantly lower in infants with NPE-AM compared to infants with the SBI (p < 0.001) and similar to the means in infants with NBI (p = 0.848, 0.098 and 0.764 respectively). A high proportion of bloody tap 346/784 (53.1%) was detected. Infants with NPE-AM were more likely to be treated with antibiotics than infants with NBIs (88.9% vs 50.7%, p < 0.001), similarly to infants with SBIs (p = 0.571).

Conclusions: The clinical presentation of infants with NPE-AM that could mimic bacterial infection and the high rate of bloody taps may lead to more hospital admissions and antibiotic prescriptions. Rapid molecular testing for detection of NPE may be of additional value in the evaluation of febrile infants.

Keywords: Aseptic meningitis; Infants; Non-polio enterovirus; Serious bacterial infection.

MeSH terms

Adult
Bacteria
Bacterial Infections*
Enterovirus Infections* / diagnosis
Enterovirus Infections* / epidemiology
Enterovirus*
Humans
Infant
Meningitis, Aseptic* / diagnosis
Meningitis, Aseptic* / epidemiology
Meningitis, Viral*
Retrospective Studies
Virus Diseases*